BACKGROUND: Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study. MATERIAL/METHODS: SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment. RESULTS: Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis. CONCLUSIONS: In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.

• MeSH
• atorvastatin aplikace a dávkování   škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• diabetes mellitus epidemiologie   MeSH
• dyslipidemie farmakoterapie   genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• hepatocyty metabolismus   MeSH
• jednonukleotidový polymorfismus * MeSH
• kouření epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• modely genetické MeSH
• myalgie chemicky indukované   epidemiologie   genetika   MeSH
• nemoci svalů chemicky indukované   epidemiologie   genetika   MeSH
• obezita epidemiologie   MeSH
• polypeptid C přenášející organické anionty MeSH
• přenašeče organických aniontů genetika   fyziologie   MeSH
• senioři MeSH
• simvastatin aplikace a dávkování   škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• statiny aplikace a dávkování   škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• atorvastatin MeSH
• polypeptid C přenášející organické anionty MeSH
• přenašeče organických aniontů MeSH
• simvastatin MeSH
• SLCO1B1 protein, human MeSH Prohlížeč
• statiny MeSH

BACKGROUND: The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS. METHODS: Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci. RESULTS: Distribution of rs6535454 in patients with SAMS (GG=51.1%, GA=40.0%, AA=8.9%) did not significantly differ (p=0.33; respectively 0.32 for codominant models of the analysis) from that in the population controls (GG=48.1%, GA=45.0%, AA=6.9%) or the SAMS-unaffected patients (GG=49.8%, GA=40.3%, AA=9.7%). Similarly, neither rs4693075 was associated with SAMS (CC=36.8%, CG=48.2%, GG=15.0% in patients suffering SAMS vs. CC=36.6%, CG=47.5%, GG=15.9 in controls and CC=35.8%, CG=48.2%, GG=15.9% in symptom-free patients, p=0.94 and 0.95 for codominant models of the analysis). Also, the haplotype distributions were not significantly different between the groups analyzed. CONCLUSIONS: The polymorphisms of the COQ2 gene do not associate with SAMS in the Czech patients treated with low doses of statins. This is another clue that the coenzyme Q10 pathway is not the most important for the development of SAMS.

• Klíčová slova
• COQ2, coenzyme Q10, myalgia, myopathy, polymorphism, statin,
• MeSH
• běloši genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genotyp MeSH
• haplotypy MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci svalů chemicky indukované   epidemiologie   genetika   MeSH
• polymorfismus genetický genetika   MeSH
• statiny škodlivé účinky   MeSH
• studie případů a kontrol MeSH
• ubichinon genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• statiny MeSH
• ubichinon MeSH
• Ubiquinone Q2 MeSH Prohlížeč

Although statin therapy has proven to be the cornerstone for prevention and treatment of cardiovascular disease (CVD), there are many patients for whom long-term therapy remains suboptimal. The aims of this article are to review the current complex issues associated with statin use and to explore when novel treatment approaches should be considered. Statin discontinuation as well as adherence to statin therapy remain two of the greatest challenges for lipidologists. Evidence suggests that between 40 and 75% of patients discontinue their statin therapy within one year after initiation. Furthermore, whilst the reasons for persistence with statin therapy are complex, evidence shows that low-adherence to statins negatively impacts clinical outcomes and residual CV risk remains a major concern. Non-adherence or lack of persistence with long-term statin therapy in real-life may be the main cause of inadequate low density lipoprotein cholesterol lowering with statins. There is a large need for the improvement of the use of statins, which have good safety profiles and are inexpensive. On the other hand, in a non-cost-constrained environment, proprotein convertase subtilisin/kexin type 9 inhibitors should arguably be used more often in those patients in whom treatment with statins remains unsatisfactory.

• Klíčová slova
• Cardiovascular risk, Discontinuation, HDL-C, Non-adherence, PCSK9, Statin, Statin-associated muscle symptoms,
• MeSH
• adherence k farmakoterapii * MeSH
• HDL-cholesterol antagonisté a inhibitory   krev   MeSH
• hypercholesterolemie krev   farmakoterapie   MeSH
• kardiovaskulární nemoci krev   farmakoterapie   MeSH
• lidé MeSH
• myalgie chemicky indukované   MeSH
• PCSK9 inhibitory MeSH
• poruchy spánku a bdění chemicky indukované   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• rizikové faktory MeSH
• statiny škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• HDL-cholesterol MeSH
• PCSK9 inhibitory MeSH
• PCSK9 protein, human MeSH Prohlížeč
• statiny MeSH

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10-15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.

• Klíčová slova
• definition, muscle symptoms, risk factors, statin intolerance,
• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: In our pilot study, we aimed to determine how many patients with the statin intolerance history referred to the specialized center for the diagnostics and treatment of lipoprotein metabolism disorders really suffer from a complete statin intolerance. The purpose of the study was to prove that complete statin intolerance is overestimated and overdiagnosed, and with the detailed knowledge of the issue and patient approach, it is possible to find an appropriate statin treatment for the most of patients. RECENT FINDINGS: With the increasing number of statin users worldwide, the issue of statin intolerance has been a frequently discussed topic in recent years. There are many factors that play a role in the manifestation of statin intolerance (predisposing factors as age, sex, and some diseases), genetic factors leading to a different metabolism, drug-drug interactions, psychological reasons, and the negative influence of the mass media. However, it is estimated that true complete statin intolerance, defined by an intolerance of at least three statins at their usual lowest daily doses, occurs in approximately 3-6% of all statin users. In our pilot study, we conducted a retrospective analysis of 300 patients who were referred to the Center of Preventive Cardiology with a history of statin intolerance. During the follow-up treatment, 222 patients (74%) were able to use some statin (rosu-, atorva-, simva-, fluvastatin), and in 21% of the cases (63 patient), the target values according their CV risk level were even achieved. Only 78 patients (26%) were confirmed as being complete statin intolerant following a thorough therapeutic effort. The most tolerated statin was rosuvastatin.

• Klíčová slova
• Complete statin intolerance, Partial statin intolerance, Statin associated muscle symptoms,
• MeSH
• kardiovaskulární nemoci prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• pilotní projekty MeSH
• primární prevence MeSH
• retrospektivní studie MeSH
• rosuvastatin kalcium škodlivé účinky   MeSH
• sekundární prevence MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• statiny škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• rosuvastatin kalcium MeSH
• statiny MeSH

Muscle problems and other adverse symptoms associated with statin use are frequent reasons for non-adherence and discontinuation of statin therapy, which results in inadequate control of hyperlipidemia and increased cardiovascular risk. However, most patients who experience adverse symptoms during statin use are able to tolerate at least some degree of statin therapy. Given the profound cardiovascular benefits derived from statins, an adequate practical approach to statin intolerance is, therefore, of great clinical importance. Statin intolerance can be defined as the occurrence of myalgia or other adverse symptoms that are attributed to statin therapy and that lead to its discontinuation. In reality, these symptoms are actually unrelated to statin use in many patients, especially in those with atypical presentations following long periods of treatment. Thus, the first step in approaching patients with adverse symptoms during the course of statin therapy is identification of those patients for whom true statin intolerance is unlikely, since most of these patients would probably be capable of tolerating adequate statin therapy. In patients with statin intolerance, an altered dosing regimen of very low doses of statins should be attempted and, if tolerated, should gradually be increased to achieve the highest tolerable doses. In addition, other lipid-lowering drugs may be needed, either in combination with statins, or alone, if statins are not tolerated at all. Stringent control of other risk factors can aid in reducing cardiovascular risk if attaining lipid treatment goals proves difficult.

• Klíčová slova
• Low-dose statin therapy, Muscle side effects, Myalgia, Statin, Statin intolerance,
• MeSH
• hyperlipidemie farmakoterapie   MeSH
• kardiovaskulární nemoci farmakoterapie   MeSH
• lidé MeSH
• myalgie chemicky indukované   MeSH
• rizikové faktory MeSH
• statiny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• tolerance léku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• statiny MeSH

INTRODUCTION: Statin intolerance (SI) occurs in patients with dyslipidemia treated with statins. Statin-associated symptoms have been reported, but the overall patient experience is poorly understood. No instruments are available to collect this patient experience. Our aim is to develop a patient survey to define SI from the patient's perspective, inform clinical practice, and identify potential patient characteristics and barriers associated with discontinuing treatment when statin-related difficulties are encountered. METHODS: We conducted qualitative concept elicitation interviews with 65 patients across 12 European study sites. A semi-structured qualitative interview guide was developed based on literature review and clinician interviews. Concept elicitation interviews with patients were used to describe the patient experience and develop the conceptual framework for the survey. RESULTS: Symptoms experienced by patients included muscle and non-muscle-related pain and discomfort; other muscle-related symptoms; gastrointestinal, cardiovascular, cold-like, fatigue-related, and sensory and systems symptoms; mood changes; and cognitive and memory problems. Impacts included limitations on general physical functioning; physical activities; social functioning; emotional impacts; sleep disturbances; decreased productivity; and increased healthcare use. Conceptual framework elements to support survey goals include demographic and clinical characteristics, health information and beliefs, statin side-effect history, symptom severity, and impact severity. CONCLUSIONS: Symptoms and impacts described by patients showed a wider range of symptoms and impacts than usually discussed clinically. The patient survey is designed to capture information from patients who experience difficulties with statin therapy and may be useful in identifying patients who are at higher risk for giving up or discontinuing their treatment. FUNDING: Amgen Inc.

• Klíčová slova
• Cardiology, Dyslipidemia, Lipid-lowering therapy, Patient experience, Qualitative research, Statin, Survey,
• MeSH
• anticholesteremika škodlivé účinky   terapeutické užití   MeSH
• bolest chemicky indukované   MeSH
• dospělí MeSH
• dyslipidemie farmakoterapie   epidemiologie   MeSH
• kvalitativní výzkum MeSH
• lidé středního věku MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• spokojenost pacientů statistika a číselné údaje   MeSH
• statiny škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• anticholesteremika MeSH
• statiny MeSH

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.

• Klíčová slova
• cardiovascular risk, dyslipidemia, nutraceuticals, position paper, statin intolerance,
• MeSH
• dyslipidemie dietoterapie   farmakoterapie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• potravní doplňky * MeSH
• statiny škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• statiny MeSH